tbuckley/cabot-search huggingface dataset:
Implementation of electronic patient-reported outcomes in head and neck oncology at a comprehensive cancer center.
Authors: Nadine Jackson McCleary, Rosh K Sethi, Ravindra Uppaluri, Sarah Whittaker, Jessica Cleveland, Brittany Black, Sunyi Zhang, Michael J. Hassett, Laura A. Goguen
Journal: Journal of Clinical Oncology (2022)

12115 Background: Monitoring electronic patient reported outcomes (ePROs) has demonstrated impact on quality of life and survival in oncology. Maintaining high response rates to ePRO measures is critical in routine care. We evaluate the routine care implementation of head and neck oncology (HNO)-focused ePROs and the impact of patient demographics and assignment method on response rate. Methods: Since October 2021, patients diagnosed with head and neck cancer (PHN) at Dana-Farber Cancer Institute (DFCI) have had the opportunity to respond to the EHR-integrated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC QLQ- H&amp;N43) at clinic visits, not to exceed every 30 days. PHN are also prompted at 7 and 14 days postoperative, regardless of clinic visit. HNO clinicians selected EORTC QLQ- H&amp;N43 because of its actionable scores and limited overlap with cross-cutting ePRO tools at DFCI. Reviewed by Patient and Family Advisory Council members, PHN can respond to the questionnaire in English or Spanish via any internet-enabled device or tablet provided in clinic. Tablet assignment rates are sent via automated report to the HNO clinic manager. Results: Between October 2021 and January 2022, PHN responded to 64% of questionnaires for eligible clinic visits (1618/2535). Post-operatively, 65% of PHN responded to EORTC QLQ- H&amp;N43 at least once within 28 days of surgery. Prompted at 7 and 14 days, PHN responded to 44% (133/300) of all post-operative questionnaires. Overall, PHN responded on their own device 50% of the time and on tablets in clinic 50% of the time. Response rates significantly associated with race, primary language, and age at clinic, but not post-operatively due to low sample size. PHN with a primary language other than English, older PHN, and PHN with races other than white responded less frequently, with the exception of Asian PHN in clinic who had the highest response rates. Clinician champions, EHR-integration, and a timely feedback loop to clinic managers facilitated response rates. Conclusions: Successful implementation of HNO ePROs is aided by clinical engagement and availability of real-time response rate data. ePRO response rate in HNO was found to be associated with race, primary language, age, and assignment method. Further work to focus on improving disparities within response rates and linking automatic interventions to scores is needed. [Table: see text]
Sequential first-line treatment with gemcitabine plus nab-paclitaxel (GA) followed by FOLFIRINOX (FFX) versus FFX alone in patients with metastatic pancreatic cancer (PC): GABRINOX-2 randomized phase 2 trial.
Authors: Fabienne Portales, Eric Assenat, Emmanuelle Samalin, Thibault Mazard, Antoine Adenis, Blandine Suchet Gallet, Catherine Fiess, Aurore Moussion, Stephanie Delaine, Florin Grigorescu, Sophie Gourgou, Marc Ychou
Journal: Journal of Clinical Oncology (2022)

TPS4190 Background: PC is a major health concern worldwide and a deadly disease due to its high metastatic behavior. In recent years, incremental progresses have been made with the use of new chemotherapy (CT) regimen in the metastatic setting. Thus, both PRODIGE 4/ACCORD11 (Conroy T, et al. 2011) and MPACT (Von Hoff D, et al. 2013) phase III trials established 2 new standard-of-care in the first line treatment of metastatic PC (mPC), demonstrating a survival benefit over gemcitabine monotherapy, with the use of FFX or GA. In the phase I/II GABRINOX trial (Assenat E, et al. ESMO Open 2021), we reported that sequential GA followed by FFX provided a high overall response rate (ORR) (64.9%) and a promising median progression-free survival (PFS, 10.5 months) and median overall survival (OS, 15.1 months), together with acceptable toxicity and remarkably low severe neurotoxicity rate (gr.3: 5.3%). To follow up these encouraging results in a controlled study, we aimed at comparing our experimental GABRINOX regimen to control FFX in the GABRINOX-2 randomized phase 2 trial (NCT05065801). Our primary objective is PFS, and our secondary objectives are tolerance, ORR, disease-control rate, OS, and Quality-of-life. Methods: Main inclusion criteria were as follows: Patients (pts) in good condition (ECOG PS ≤ 1), aged from 18 to 75 yo, with histologically or cytological proven mPC and at least one measurable metastatic target. Pts should have not been treated with (adjuvant) chemotherapy in the last 6 months. Eligible pts are randomized (ratio 1:1) either in the standard FFX group or in the experimental GABRINOX group where a GA (gemcitabine 1000 mg/m² and Nab-paclitaxel 125 mg/m², day 1-8-15) cycle alternates after a 2-weeks rest with a FFX cycle. To detect an increase in median PFS from 6.4 to 10.5 months (HR = 0.61) with a 80% power and a 5% α risk, 130 events are required among a total population of 210 pts. PFS was defined as the length of time between randomization and the onset of 1 st documented progression (RECIST 1.1 criteria) or death. The study of quality of life will use the EORTC QLQ-C30 and QLQ-PAN26 self-reported questionnaires at baseline and every 2 months up to 12 months and then at 16, 20 and 24 months. Circulating DNA tests will be carried out at baseline and every 2 months until progression. All numerical variables will be expressed as medians and 95% CI, while PFS and OS will be estimated using Kaplan-Meier method. Multivariate analyses will use Cox proportional hazard model. Enrolment started in late 2021 and 3 patients were included so far. Clinical trial information: NCT05065801.
Does centralized revision of prostate biopsy impact on active surveillance outcomes? Results from a single, high-volume institution series
Authors: R. Leni, S. Scuderi, G. Gandaglia, R. Lucianò, N. Tenace, F. Paparesta, L. Pepi, L. Nocera, D. Robesti, L. Quarta, L. Toneatto, A. Stabile, E. Mazzone, F. Barletta, A. Cimadamore, R. Montironi, P.I. Karakiewicz, S. Shariat, F. Dehò, F. Montorsi, A. Briganti
Journal: European Urology (2022)
NFB-08. TRAM-01: A Phase 2 study of trametinib for pediatric patients with neurofibromatosis type 1 and plexiform neurofibromas
Authors: Dorsa Sadat Kiaei, Valérie Larouche, Jean-Claude Décarie, Uri Tabori, Cynthia Hawkin, Sarah Lippé, Benjamin Ellezam, Luis H Ospina, Yves Théoret, Léandra Desjardins, Marie-Élaine Métras, Serge Sultan, Édith Cantin, Marie-Ève Routhier, Chantal Mailloux, Marie-Claude Bertrand, Maxime Caru, Stéphanie Vairy, Geneviève Legault, Éric Bouffet, Vijay Ramaswamy, Hallie Coltin, Lucie Lafay-Cousin, Juliette Hukin, Craig Erker, Nada Jabado, Mathieu Dehaes, Sébastien Perreault
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Plexiform neurofibromas (PN) are found in up to 50% of patients with neurofibromatosis type 1 (NF1). Trametinib has been used widely to treat PN but limited data has been reported on its efficacy within a clinical trial. METHODS: This ongoing multicenter phase II trial includes patients with pediatric low-grade glioma and PN. The primary objective for PN was to evaluate the overall response rate based on RECIST 1.1 criteria after daily oral trametinib administration for eighteen 28-day cycles. The volumes of PN were centrally quantified using a new semi-automatic 3D segmentation method. RESULTS: As of January 1, 2022, 45 patients with PN were enrolled in the study. Twenty-eight completed treatment and were available for analysis. For these patients, the median age was 11.4 years (range 0.7-19.8) including 16 males (57.1%). The majority did not receive prior systemic therapies (71.4%). The median volume of PN at baseline was 49.5 cm3 (range 2.6 to 469). Among the 28 patients, 25 (89.3%) completed 18 cycles as planned. One patient discontinued due to adverse reaction, one patient refused to continue treatment and one patient discontinued treatment based on physician decision. Median duration of treatment was 15.9 months (range 4.6 to 16.8). Median duration of follow-up was 29.7 months (range 17.7 to 38.1). A total of 32 PN were available for volumetric analysis. Using RECIST evaluation, the overall response rate was 24.1%. Volumetric assessment demonstrated an overall response rate of 60.7% and 62.5% of PN showed a decrease of more than 20% in volume. Median decrease in volume was -30% (range -93.5 to 14.3). Twenty-seven patients (93.1%) had durable response without progression (lasting ≥1 year). CONCLUSION: We report outcome and volumetric quantification of PN treated with trametinib within a large clinical trial. Based on the current results, trametinib appears effective and offers durable response.
A phase 1b study to evaluate safety, tolerability, pharmacokinetics, and efficacy of SER-155 in adults undergoing hematopoietic stem cell transplantation to reduce the risk of infection and graft versus host disease (NCT04995653).
Authors: Doris M. Ponce, Mary-Jane Lombardo, Christopher B. Ford, Jonathan U. Peled, Marcel R. M. Van Den Brink, Bindu Tejura
Journal: Journal of Clinical Oncology (2022)

TPS7074 Background:In patients undergoing allogeneic hematopoietic stem cell transplantation (HCT), loss of gastrointestinal microbial diversity is associated with risk of bloodstream infections (BSI), acute graft-versus-host disease (aGvHD), and death. SER-155 is a cultivated investigational microbiome therapeutic rationally designed to improve clinical outcomes in patients undergoing HCT by restoring colonization resistance to pathobionts, promoting epithelial barrier integrity, and reducing colonic inflammation. SER-155-001 is a Phase 1b study to evaluate the efficacy, safety, and pharmacokinetics (PK) of SER-155 in adults undergoing HCT. Methods:This study will enroll approximately 70 subjects ≥ 18 years in an open-label Cohort 1 (n = 10) followed by a double-blind, placebo-controlled Cohort 2 (n = 60) randomized 1:1 to SER-155 or placebo and stratified by conditioning regimen intensity. Exclusion criteria include history of severe colitis of any etiology or active inflammatory bowel disease or total colectomy, transplant using umbilical cord blood or ex vivo T-cell therapy, receipt of fecal microbiota transplant or any live microbial therapeutic within 3 months prior to screening, and evidence of relapse or progression of hematologic malignancy (minimal residual disease is allowed). Following screening, subjects in both cohorts will receive 2 treatment courses (before and after HCT), each comprised of microbiome conditioning with oral vancomycin or placebo followed by SER-155 or placebo, and a conditional 3rd treatment course if the subject receives antibiotics (Table). Safety outcomes will be followed through 52 weeks post HCT. The primary endpoint is to evaluate the incidence and severity of adverse events, serious adverse events, and adverse events of special interest. Secondary endpoints include rates of BSI, gastrointestinal infections, aGvHD, febrile neutropenia and overall survival in placebo vs SER-155 arms. Microbiome related endpoints include engraftment of SER-155 bacterial strains in the gastrointestinal tract (PK endpoint) and fecal microbiome diversity, composition and metabolites. Clinical trial information: NCT04995653. [Table: see text]
Extension of cervical screening intervals with primary human papillomavirus testing: observational study of English screening pilot data
Authors: Matejka Rebolj, Kate Cuschieri, Christopher S Mathews, Francesca Pesola, Karin Denton, Henry Kitchener
Journal: BMJ (2022)

Abstract Objectives To provide updated evidence about the risk of cervical intraepithelial neoplasia grade 3 or higher (CIN3+) and cervical cancer after a negative human papillomavirus (HPV) test in primary cervical screening, by age group and test assay. Design Observational study. Setting Real world data from the English HPV screening pilot’s first and second rounds (2013-16, follow-up to end of 2019). Participants 1 341 584 women. Interventions Cervical screening with HPV testing or liquid based cytological testing (cytology or smear tests). Women screened with cytology were referred to colposcopy after high grade cytological abnormalities or after borderline or low grade abnormalities combined with a positive HPV triage test. Women screened with HPV testing who were positive were referred at baseline if their cytology triage test showed at least borderline abnormalities or after a retest (early recall) at 12 and 24 months if they had persistent abnormalities. Main outcome measures Detection of CIN3+ and cervical cancer after a negative HPV test. Results For women younger than 50 years, second round detection of CIN3+ in this study was significantly lower after a negative HPV screen in the first round than after cytology testing (1.21/1000 v 4.52/1000 women screened, adjusted odds ratio 0.26, 95% confidence interval 0.23 to 0.30), as was the risk of interval cervical cancer (1.31/100 000 v 2.90/100 000 woman years, adjusted hazard ratio 0.44, 0.23 to 0.84). Risk of an incident CIN3+ detected at the second screening round in the pilot five years after a negative HPV test was even lower in women older than 50 years, than in three years in women younger than 50 years (0.57/1000 v 1.21/1000 women screened, adjusted odds ratio 0.46, 0.27 to 0.79). Women with negative HPV tests at early recall after a positive HPV screening test without cytological abnormalities had a higher detection rate of CIN3+ at the second routine recall than women who initially tested HPV negative (5.39/1000 v 1.21/1000 women screened, adjusted odds ratio 3.27, 95% confidence interval 2.21 to 4.84). Detection after a negative result on a clinically validated APTIMA mRNA HPV test was similar to that after clinically validated cobas and RealTime DNA tests (for CIN3+ at the second round 1.32/1000 v 1.14/1000 women screened, adjusted odds ratio 1.05, 0.73 to 1.50). Conclusions These data support an extension of the screening intervals, regardless of the test assay used: to five years after a negative HPV test in women aged 25-49 years, and even longer for women aged 50 years and older. The screening interval for HPV positive women who have negative HPV tests at early recall should be kept at three years.
Genetic ancestry correlates of the cancer somatic mutational landscape from tumor profiling data of 50,000 patients with cancer.
Authors: Francisco De La Vega, Brooke Rhead, Yannick Pouliot, Justin Guinney
Journal: Journal of Clinical Oncology (2022)

10573 Background: The incidence and mortality of cancer vary widely across race and ethnicity. This is attributed to an interplay of socioeconomic factors, environmental exposures, and genetic background. Cancer genomic studies have underrepresented minorities and individuals of non-European descent, thus limiting a comprehensive understanding of disparities in the diagnosis, prognosis, and treatment of cancer among these populations. Furthermore, the social constructs of race and ethnicity are far from precise categories to understand the biological underpinnings of such differences. In this study, we use a large real-world data (RWD) patient cohort to examine associations of genetic ancestry with somatic alterations in known cancer driver genes. Methods: We inferred genetic ancestry from approximately 50,000 de-identified records from cancer patients of diverse histology who underwent tumor genomic profiling with the Tempus xT next-generation sequencing (NGS) assay. Our cohort includes patients with brain, breast, colorectal, hematopoietic, lung, and ovarian cancers, among others. We used 654 ancestry informative markers selected to overlap the target regions of the 648-gene Tempus xT NGS assay to infer global ancestry proportions at the continental level: Africa (AFR), America (AMR), Europe (EUR), East Asia (EAS), and South Asia (SAS). We imputed race/ethnicity categories using ancestry proportions on subjects lacking such metadata. Results: Most patients were of European descent (72%), however, continental genetic ancestry inference identified 4.7 and 3.8-fold more patients with substantial (&gt; 50%) AFR and AMR ancestry, correspondingly, compared with TCGA. We observed higher percentages of AFR ancestry patients with prostate, breast, and colorectal cancer (1.8-3.1%) and AMR ancestry patients with colorectal cancer (2.4%) compared to the overall cohort-level distributions (p &lt; 0.05). Using imputation, we identified 60% and 121% more patients as likely Black and Hispanic/Latino, respectively. We observed several associations between genetic ancestry with tumor mutation burden (TMB), e.g., a reduction in median TMB in Asian breast cancer patients (Asian TMB mean = 2.3 m/Mb vs 4.4 for Black, 3.3 for Hispanic, and 4.2 for White; p &lt; 0.0001), in paired tumor/normal sequencing data. Furthermore, we found associations between ancestry and nonsynonymous somatic mutations in cancer genes, e.g. in CTNNB1 with EAS ancestry (OR = 1.18) and EGFR with EAS (OR = 1.24), AMR (OR = 1.30), and EUR (OR = 0.89) ancestries (all p &lt; 0.001) in lung cancer patients. Conclusions: Our results support the use of genetic ancestry inference on RWD to improve upon the social constructs of race and ethnicity, allowing us to better understand the impact of shared germline genetic or exposure backgrounds into cancer mutational processes that influence incidence, progression, and outcomes.
GCT-03. MonoGerm: A proposed phase II trial of carboplatin or vinblastine monotherapy induction prior to radiotherapy for intracranial germinoma
Authors: Matthew Murray, John Apps, Anna Lawson, Laura Kirton, Andrew Peet, Theodoros Arvanitis, Lorna Fern, Dipayan Mitra, Nicholas Coleman, Thankamma Ajithkumar, Brigitte Bison, Gareth Veal, Daniel Stark, Giovanni Morana, James Nicholson, Lucinda Billingham
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Intracranial germinoma is chemosensitive but radiotherapy (RT) is needed for cure. In localised disease, three-drug standard-of-care (SOC) inpatient chemotherapy is used to reduce RT fields/dose. Concomitant diabetes insipidus is common, making chemotherapy delivery challenging. Small studies have demonstrated benefits from single-agent carboplatin or vinblastine in germinoma as an alternative to SOC. However, this needs prospective evaluation in a clinical trial. METHODS: We developed a trial, with a patient-public-involvement workstream, primarily evaluating whether single-agent chemotherapy (carboplatin or vinblastine) is non-inferior to SOC for inducing radiological complete response (CR) in localised disease, and is associated with reduced toxicity and improved quality-of-life (QoL), evaluated through patient-reported-outcome-measures (PROMs). RESULTS: The resultant proposed multi-centre, phase II proof-of-principle trial will investigate, in parallel, two single agents as monotherapy induction, in children/teenagers/adults with intracranial germinoma. Trial features include: a) Bayesian statistical design determining whether CR rate for either agent is sufficiently non-inferior to SOC; b) ‘Flip-flop’ design with alternating, continuous enrolment to the two single-agents, interim assessments after each recruited cohort, and early stopping rules for inferiority; c) Safety MRI, after 6-weeks of chemotherapy with real-time central-radiological-review; d) Proof-of-principle vinblastine monotherapy arm for metastatic patients awaiting definitive craniospinal-irradiation; e) State-of-the-art integrated imaging acquisition, QoL/PROM, pharmacokinetics and circulating microRNA studies to maximise information/learning; f) European and North American neuroradiological response criteria comparison and prospective evaluation of new consensus criteria. CONCLUSIONS: Trial results will: a) establish whether monotherapy is a treatment option in this setting, which may be practice-altering; b) use QoL/PROM data to inform on optimal treatment if results similar; c) use embedded radiological assessments to develop intracranial germinoma trials and facilitate European/US study comparisons; d) describe vinblastine pharmacokinetic data to inform future dosing schedules in this and other malignancies; and e) quantify circulating microRNAs, facilitating future non-invasive diagnosis/risk-stratification.
Germline screening rates and patterns for patients with pancreatic cancer at an academic medical center.
Authors: DeJuana Coleman, Martha Thomas, Tri Minh Le, Paul Raymond Kunk, Matthew Reilley
Journal: Journal of Clinical Oncology (2022)

10590 Background: Current National Comprehensive Cancer Network guidelines recommend germline genetic testing for all pancreatic cancer patients irrespective of family history. Germline testing provides insight on inherited pathogenic variants that may influence care. Approximately 10% of pancreatic adenocarcinoma (PDAC) patients have pathogenic mutations which may have treatment implications and warrant the introduction of targeted therapy approaches. Patients with germline BRCA1/2 or PALB2 mutations have increased sensitivity to platinum chemotherapy and PARP-inhibitor therapies. Germline testing results may have important implications for patients’ family members for earlier targeted screening. A better understanding of the current state of testing is needed to develop systems to improve screening rates. We conducted a retrospective review of clinical practice patterns at an academic cancer center to assess the current uptake. Methods: Patients with pancreatic adenocarcinoma seen at the University of Virginia Health System within the 2021 calendar year were identified. Retrospective review of genetic counseling referral and germline genomic screening for individual patients was performed. Results: 210 patients with pancreatic adenocarcinoma were identified. 39 (19%) PDAC patients had a referral to genetic counseling placed in the electronic medical record and 44 (21%) completed germline screening. Of the patients referred to genetics, 17/39 patients (44%) met with a genetic counselor which led to germline screening, 3/39 (8%) patients were referred and saw genetics after receiving germline testing results. Among patients who completed germline screening, 27/44 (61%) had testing initially ordered by their oncologist with referral to genetic counseling based on testing results 3/27 (11%). Conclusions: Despite guideline recommendations, germline testing rates are low among this PDAC population. Genetic counselors are essential members of a multidisciplinary team and guide patient discussions and decision making with regards to germline testing. Typical practice has involved referral to meet with a genetics counselor prior to testing; however many patients elect not to schedule a visit and consequently do not obtain germline screening. Barriers may include costs associated with genetic counseling/testing, time constraints, and patient understanding of the relevance of testing for their cancer care. We observed that offering germline testing to PDAC patients with referral to genetic counseling based on results and patient preference is a viable practice pattern. Upfront clinician driven germline testing may offer an opportunity to improve access to germline screening. Prospective clinical trials are needed to increase rates of germline testing and genetic counseling for PDAC patients.
Radiation exposure using lead-lined versus regular latex surgical gloves during endourological procedures: A single-center prospective comparative study
Authors: A. Bravo-Balado, E. Emiliani, A-K. Kanashiro, J. Balañà, S. Fontanet, A. Skolarikos, F. Sánchez-Martín, F. Millán, O. Angerri
Journal: European Urology (2022)